Hydrogel-Encapsulated Beads Enable Proximity-Driven Encoded Library Synthesis and Screening
نویسندگان
چکیده
Encoded combinatorial library technologies have dramatically expanded the chemical space for screening but are usually only analyzed by affinity selection binding. It would be highly advantageous to reformat outputs ”one-bead-one-compound” solid-phase libraries, unlocking activity-based and cellular capabilities. Here, we describe hydrogel-encapsulated magnetic beads that enable such a transformation. Bulk emulsion polymerization of polyacrylamide hydrogel shells around microbeads yielded uniform particles (7 ± 2 μm diameter) compatible with diverse in-gel functionalization (amine, alkyne, oligonucleotides) transformations associated DNA-encoded synthesis (acylation, enzymatic DNA ligation). In case study reformatting mRNA display transcription from DNA-templated encapsulated in gel colocalized both RNA via hybridization copolymerized complementary translation puromycin labeling. Two control epitope templates (V5, HA) were successfully enriched (50- 99-fold, respectively) an NNK5 bead screen FACS. Proximity-driven concert sample manipulation provides plausible means encoded libraries at scale.
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ژورنال
عنوان ژورنال: ACS central science
سال: 2023
ISSN: ['2374-7951', '2374-7943']
DOI: https://doi.org/10.1021/acscentsci.3c00316